tbuckley/cabot-search huggingface dataset:
CD73 and PD-L1 dual blockade amplifies antitumor efficacy of SBRT in murine PDAC models
Authors: Jian Ye, Nicholas W Gavras, David C Keeley, Angela L Hughson, Gary Hannon, Tara G Vrooman, Maggie L Lesch, Carl J Johnston, Edith M Lord, Brian A Belt, David C Linehan, Jim Eyles, Scott A Gerber
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Stereotactic body radiotherapy (SBRT) induces immunogenic cell death, leading to subsequent antitumor immune response that is in part counterbalanced by activation of immune evasive processes, for example, upregulation of programmed cell death-ligand 1 (PD-L1) and adenosine generating enzyme, CD73. CD73 is upregulated in pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissue and high expression of CD73 in PDACs is associated with increased tumor size, advanced stage, lymph node involvement, metastasis, PD-L1 expression and poor prognosis. Therefore, we hypothesized that blockade of both CD73 and PD-L1 in combination with SBRT might improve antitumor efficacy in an orthotopic murine PDAC model. Methods We assessed the combination of systemic blockade of CD73/PD-L1 and local SBRT on tumor growth in primary pancreatic tumors, and investigated systemic antitumor immunity using a metastatic murine model bearing both orthotopic primary pancreatic tumor and distal hepatic metastases. Immune response was quantified by flow cytometric and Luminex analyses. Results We demonstrated that blockade of both CD73 and PD-L1 significantly amplified the antitumor effect of SBRT, leading to superior survival. The triple therapy (SBRT+anti-CD73+anti-PD-L1) modulated tumor-infiltrating immune cells with increases of interferon-γ + CD8 + T cells. Additionally, triple therapy reprogramed the profile of cytokines/chemokines in the tumor microenvironment toward a more immunostimulatory phenotype. The beneficial effects of triple therapy are completely abrogated by depletion of CD8 + T cells, and partially reversed by depletion of CD4 + T cells. Triple therapy promoted systemic antitumor responses illustrated by: (1) potent long-term antitumor memory and (2) enhanced both primary and liver metastases control along with prolonged survival.
Mpox: an updated review of dermatological manifestations in the current outbreak
Authors: Carlo Alberto Maronese, Gianluca Avallone, Italo Francesco Aromolo, Cristina Beatrice Spigariolo, Eleonora Quattri, Stefano Ramoni, Carlo Giovanni Carrera, Angelo Valerio Marzano
Journal: British Journal of Dermatology (2023)

Abstract Mpox is a disease caused by a double-stranded DNA orthopoxvirus discovered in 1958. In 2022, an outbreak on an unprecedented scale marked its transition from neglected, zoonotic disease circulating almost exclusively within African borders to sexually transmitted infection (STI) of international concern. Although phylogenetic evidence suggests progressive evolution from the strain associated with the 2018 outbreak in Nigeria, epidemiological links with previous cases have still not been completely elucidated. Clinically, mpox presents with systemic symptoms, such as fever, headache, malaise and a characteristic cutaneous eruption, similar to that of cognate viruses (e.g. smallpox). Mpox pseudopustules evolve through several stages, including umbilication and crusting, and resolve in the span of 2–3 weeks. The hallmarks that set the 2022 outbreak apart from classic mpox were a disproportionate number of cases occurring in men who have sex with men, an often localized cutaneous picture and a significant burden in terms of concomitant STIs. Investigations into the disease pathogenesis, related immune response, clinical and dermoscopic features, in addition to studies aimed at defining novel management strategies, have advanced mpox knowledge considerably. Herein, recent findings on mpox are reviewed, with a keen focus on dermatological manifestations and their implications in the current diagnostic scenario, reinforcing the pivotal role of dermatologists in managing suspect cases and preventing further spread of the contagion.
Vaccine-induced correlate of protection against fatal COVID-19 in older and frail adults during waves of neutralization-resistant variants of concern: an observational study
Authors: Linnea Vikström, Peter Fjällström, Yong-Dae Gwon, Daniel J. Sheward, Julia Wigren-Byström, Magnus Evander, Oscar Bladh, Micael Widerström, Christian Molnar, Gunlög Rasmussen, Louise Bennet, Mikael Åberg, Jonas Björk, Staffan Tevell, Charlotte Thålin, Kim Blom, Jonas Klingström, Ben Murrell, Clas Ahlm, Johan Normark, Anders F. Johansson, Mattias N.E. Forsell
Journal: The Lancet Regional Health - Europe (2023)

To inform future preventive measures including repeated vaccinations, we have searched for a clinically useful immune correlate of protection against fatal COVID-19 among nursing homes residents.We performed repeated capillary blood sampling with analysis of S-binding IgG in an open cohort of nursing home residents in Sweden. We analyzed immunological and registry data from 16 September 2021 to 31 August 2022 with follow-up of deaths to 30 September 2022. The study period included implementation of the 3rd and 4th mRNA monovalent vaccine doses and Omicron virus waves.A total of 3012 nursing home residents with median age 86 were enrolled. The 3rd mRNA dose elicited a 99-fold relative increase of S-binding IgG in blood and corresponding increase of neutralizing antibodies. The 4th mRNA vaccine dose boosted levels 3.8-fold. Half-life of S-binding IgG was 72 days. A total 528 residents acquired their first SARS-CoV-2 infection after the 3rd or the 4th vaccine dose and the associated 30-day mortality was 9.1%. We found no indication that levels of vaccine-induced antibodies protected against infection with Omicron VOCs. In contrast, the risk of death was inversely correlated to levels of S-directed IgG below the 20th percentile. The death risk plateaued at population average above the lower 35th percentile of S-binding IgG.In the absence of neutralizing antibodies that protect from infection, quantification of S-binding IgG post vaccination may be useful to identify the most vulnerable for fatal COVID-19 among the oldest and frailest. This information is of importance for future strategies to protect vulnerable populations against neutralization resistant variants of concern.Swedish Research Council, SciLifeLab via Knut and Alice Wallenberg Foundation, VINNOVA. Swedish Healthcare Regions, and Erling Persson Foundation.
Obesity-induced changes in cancer cells and their microenvironment: Mechanisms and therapeutic perspectives to manage dysregulated lipid metabolism
Authors: Miriam Lee-Rueckert, Marina Canyelles, Mireia Tondo, Noemi Rotllan, Petri T. Kovanen, Vicenta Llorente-Cortes, Joan Carles Escolà-Gil
Journal: Seminars in Cancer Biology (2023)

Obesity has been closely related to cancer progression, recurrence, metastasis, and treatment resistance. We aim to review recent progress in the knowledge on the obese macroenvironment and the generated adipose tumor microenvironment (TME) inducing lipid metabolic dysregulation and their influence on carcinogenic processes. Visceral white adipose tissue expansion during obesity exerts systemic or macroenvironmental effects on tumor initiation, growth, and invasion by promoting inflammation, hyperinsulinemia, growth-factor release, and dyslipidemia. The dynamic relationship between cancer and stromal cells of the obese adipose TME is critical for cancer cell survival and proliferation as well. Experimental evidence shows that secreted paracrine signals from cancer cells can induce lipolysis in cancer-associated adipocytes, causing them to release free fatty acids and acquire a fibroblast-like phenotype. Such adipocyte delipidation and phenotypic change is accompanied by an increased secretion of cytokines by cancer-associated adipocytes and tumor-associated macrophages in the TME. Mechanistically, the availability of adipose TME free fatty acids and tumorigenic cytokines concomitant with the activation of angiogenic processes creates an environment that favors a shift in the cancer cells toward an aggressive phenotype associated with increased invasiveness. We conclude that restoring the aberrant metabolic alterations in the host macroenvironment and in adipose TME of obese subjects would be a therapeutic option to prevent cancer development. Several dietary, lipid-based, and oral antidiabetic pharmacological therapies could potentially prevent tumorigenic processes associated with the dysregulated lipid metabolism closely linked to obesity.
Addressing Serious Illness Care in Medicare Advantage
Authors: Claire K. Ankuda, Melissa D. Aldridge, R. Tyler Braun, Norma B. Coe, David C. Grabowski, David J. Meyers, Andrew Ryan, David Stevenson, Joan M. Teno
Journal: New England Journal of Medicine (2023)

Interview with Claire Ankuda on ensuring access to high-quality and equitable care in Medicare Advantage. (10:15)Download A comprehensive approach that prioritizes improving data transparency and quality measurement could help ensure that Medicare Advantage facilitates the delivery of high-quality and equitable care.
Perspectives on validation of clinical predictive algorithms
Authors: Anne A. H. de Hond, Vaibhavi B. Shah, Ilse M. J. Kant, Ben Van Calster, Ewout W. Steyerberg, Tina Hernandez-Boussard
Journal: npj Digital Medicine (2023)

The generalizability of predictive algorithms is of key relevance to application in clinical practice. We provide an overview of three types of generalizability, based on existing literature: temporal, geographical, and domain generalizability. These generalizability types are linked to their associated goals, methodology, and stakeholders.
Deciphering and advancing CAR T-cell therapy with single-cell sequencing technologies
Authors: Shengkang Huang, Xinyu Wang, Yu Wang, Yajing Wang, Chenglong Fang, Yazhuo Wang, Sifei Chen, Runkai Chen, Tao Lei, Yuchen Zhang, Xinjie Xu, Yuhua Li
Journal: Molecular Cancer (2023)

Abstract Chimeric antigen receptor (CAR) T-cell therapy has made remarkable progress in cancer immunotherapy, but several challenges with unclear mechanisms hinder its wide clinical application. Single-cell sequencing technologies, with the powerful unbiased analysis of cellular heterogeneity and molecular patterns at unprecedented resolution, have greatly advanced our understanding of immunology and oncology. In this review, we summarize the recent applications of single-cell sequencing technologies in CAR T-cell therapy, including the biological characteristics, the latest mechanisms of clinical response and adverse events, promising strategies that contribute to the development of CAR T-cell therapy and CAR target selection. Generally, we propose a multi-omics research mode to guide potential future research on CAR T-cell therapy.
Corporate Citizenship and Institutional Responses Post- <i>Dobbs</i> — Critical Lessons from Two Restrictive States
Authors: Justin R. Lappen, Leilah Zahedi-Spung, Ashley R. Brant
Journal: New England Journal of Medicine (2023)

In coordinating responses to new state abortion restrictions in the United States, health care organizations' interpretations of their societal obligations will affect access to care, clinical practice environments, and public health.
Intracranial injection of natural killer cells engineered with a HER2-targeted chimeric antigen receptor in patients with recurrent glioblastoma
Authors: Michael C Burger, Marie-Therese Forster, Annette Romanski, Florian Straßheimer, Jadranka Macas, Pia S Zeiner, Eike Steidl, Stefanie Herkt, Katharina J Weber, Jonathan Schupp, Jennifer H Lun, Maja I Strecker, Karolin Wlotzka, Pinar Cakmak, Corinna Opitz, Rosemol George, Iris C Mildenberger, Paulina Nowakowska, Congcong Zhang, Jasmin Röder, Elvira Müller, Kristina Ihrig, Karl-Josef Langen, Michael A Rieger, Eva Herrmann, Halvard Bonig, Patrick N Harter, Yvonne Reiss, Elke Hattingen, Franz Rödel, Karl H Plate, Torsten Tonn, Christian Senft, Joachim P Steinbach, Winfried S Wels
Journal: Neuro-Oncology (2023)

Abstract Background Glioblastoma (GB) is incurable at present without established treatment options for recurrent disease. In this phase I first-in-human clinical trial we investigated safety and feasibility of adoptive transfer of clonal chimeric antigen receptor (CAR)-NK cells (NK-92/5.28.z) targeting HER2, which is expressed at elevated levels by a subset of glioblastomas. Methods Nine patients with recurrent HER2-positive GB were treated with single doses of 1 × 107, 3 × 107, or 1 × 108 irradiated CAR-NK cells injected into the margins of the surgical cavity during relapse surgery. Imaging at baseline and follow-up, peripheral blood lymphocyte phenotyping and analyses of the immune architecture by multiplex immunohistochemistry and spatial digital profiling were performed. Results There were no dose-limiting toxicities, and none of the patients developed a cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Five patients showed stable disease after relapse surgery and CAR-NK injection that lasted 7 to 37 weeks. Four patients had progressive disease. Pseudoprogression was found at injection sites in 2 patients, suggestive of a treatment-induced immune response. For all patients, median progression-free survival was 7 weeks, and median overall survival was 31 weeks. Furthermore, the level of CD8+ T-cell infiltration in recurrent tumor tissue prior to CAR-NK cell injection positively correlated with time to progression. Conclusions Intracranial injection of HER2-targeted CAR-NK cells is feasible and safe in patients with recurrent GB. 1 × 108 NK-92/5.28.z cells was determined as the maximum feasible dose for a subsequent expansion cohort with repetitive local injections of CAR-NK cells.
Long-Term Results of Endoscopic Removal of Large Colorectal Adenomas
Authors: U Seitz, S Bohnacker, S Seewald, F Thonke, N Soehendra
Journal: Endoscopy (2003)

Background and Study Aims: Endoscopic removal of large colorectal polyps has not been widely accepted. The aims of this study were to evaluate our longterm experiences justifying endoscopic resection technique as the treatment of choice. Patients and Methods: During a period of 12 years, 288 patients with a total of 302 polyps larger than 3 cm in diameter were treated endoscopically. 224 polyps were sessile and 78 pedunculated. Sessile polyps were removed using the piecemeal technique. Surgery was recommended in patients with unfavorable histology. Patients with favorable histology were followed up at 3 – 6 month intervals in the first year and then every 1 – 2 years. Results: A total of 184 patients with sessile polyps were followed up for at least 6 months. Recurrence rate of 166 benign polyps was 17 % (29/166). Only two patients had malignant recurrence. 8 of 18 patients with malignant polyps underwent surgery while 10 were unfit for surgery. 8 of these patients remained free of recurrence. Conclusions: Previous concerns about endoscopic removal of large colorectal polyps are no longer justified. The results of this study showed that endoscopic resection of large colorectal polyps is safe and effective. In patients with high operative risk, endoscopic removal may be adequate.
Therapy of localized non-Hodgkin's lymphoma in children.
Authors: I T Magrath, C Janus, E Sariban
Journal: Journal of Clinical Oncology (1984)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1984.2.2.140 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 6699664 Therapy of localized non-Hodgkin's lymphoma in children. I T MagrathxI T MagrathSearch for articles by this author , C JanusxC JanusSearch for articles by this author , E SaribanxE SaribanSearch for articles by this author https://doi.org/10.1200/JCO.1984.2.2.140 PDF "Therapy of localized non-Hodgkin's lymphoma in children.." Journal of Clinical Oncology, 2(2), pp. 140–141© 1984 by American Society of Clinical Oncology
Abstract 21068: Far Red/Near Infrared Light Stimulates Hindlimb Collateralization via Nitric Oxide
Authors: Nicole L Lohr, James Grosek, Dorothee Weihrauch, James T Ninomiya, David Warltier
Journal: Circulation (2010)

Peripheral artery disease (PAD) has significant morbidity due to amputation associated from the development of critical limb ischemia. Present therapies are non-curative, however developing a funct...
Abstract 19057: Therapeutic Inhibition of Microrna-208a Attenuates Apoptosis, Fibrosis, and Improves Cardiac Function Post Myocardial Infarction
Authors: Hasahya Tony, Meng Kai, Wu Bangwei, Zeng Qiutang
Journal: Circulation (2014)

Introduction: MicronRNA-208a is a heart specific microRNA that regulates cardiac stress response. We investigated if Therapeutic inhibition of miR208a using antagomir attenuates apoptosis, fibrosis, and improves cardiac function post Myocardial infarction (MI). Methods and Results: Adult male C57BL/6 mice had MI induced by ligation of the Left anterior descending coronary artery (LAD) and were randomly assigned to Antagomir, Agomir, or control group. Sham group mice had the same procedure done but without ligation of the LAD. Agomir group received 20nmols of miR-208a agomir for gain of function, and antagomir group received 100nmols of miR-208a antagomir for loss of function, in 0.2mls normal saline as vehicle, while control and sham group received vehicle only. These were sacrificed at day 10 and hearts studied for Apoptosis and Fibrosis. The effect of miR-208a on apoptosis in ischemic cardiomyocytes was studied in cultured neonatal mice myocytes transfected with agomir or antagomir, and compared to cont...
Abstract 9367: Speckle-Tracking and Tissue-Doppler Stress Echocardiography in Arterial Hypertension
Authors: Kai Hensel, Henning Littwitz, Roman Leischik
Journal: Circulation (2011)

OBJECTIVE: 2D-strain (2DS) and tissue-Doppler imaging (TDI) was combined with physical stress echocardiography to assess differences in LV function between hypertensive patients and healthy controls under physical exercise. We hypothesized whether LV peak strain is an early marker to identify hypertensive patients at high risk for congestive heart failure. METHODS: Individuals with isolated arterial hypertension (n=30) who had no other cardiac or non-cardiac diseases were compared with a random collection of completely healthy controls (n=30). LV function was assessed with 2DS and TDI: At rest, low (50 Watts) and high resistance (150 Watts) of physical challenge on a bicycle. Global longitudinal (LS), circumferential (CS) and radial strain (RS) were assessed. Subsequently, intra- and inter-observer reliability analyses were performed (Bland-Altmann test) RESULTS: Compared to the hypertensive group (mean blood pressure (MBP) = 79.1 ± 13.6 mmHg), healthy volunteers (MBP = 84.5 ± 15 mmHg) were shown to have significantly higher values of CS (p=0.027) and LS (p=0.036) using 2DS at rest. At 50 Watts of resistance the same differences could be shown with a higher degree of statistical significance. At 150 Watts of resistance the control group (MBP = 119.9 ± 16.8 mmHg) had significantly higher levels of contractility in CS (p=0.023), LS (p=0.000) and RS (p=0.005) than hypertensive patients (MBP = 125.7 ± 15.1 mmHg). TDI showed similar results, while significant differences could only be proven at the highest level of physical challenge. The influence of physical challenge on cardiac strain was shown most distinctively by TDI in LS (p=0.000) and CS (p=0.007) in the control group. CONCLUSIONS: Compared to the healthy control group, patients with arterial hypertension were found to have reduced levels of left ventricular contractility. This promotes peak strain as an early parameter for LV deterioration due to arterial hypertension. In the assessment of the impact of hypertensive heart disease on LV contractility, 2DS was shown to be more sensitive for strain analysis at rest whereas TDI detected more differences in contractility under physical exercise. Given these results, quantitative deformation imaging is a promising addition to stress echocardiography.
Nontuberculous Mycobacteria
Authors: Kenneth N. Olivier, David J. Weber, Ji-Hyun Lee, Allison Handler, Gail Tudor, Paul L. Molina, Joseph Tomashefski, Michael R. Knowles
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Section:ChooseTop of pageAbstract <<METHODSRESULTSDISCUSSIONAPPENDIXReferencesCITING ARTICLES
Upregulated FoxM1 expression induced by hepatitis B virus X protein promotes tumor metastasis and indicates poor prognosis in hepatitis B virus-related hepatocellular carcinoma
Authors: Limin Xia, Wenjie Huang, Dean Tian, Hongwu Zhu, Yongguo Zhang, Hao Hu, Daiming Fan, Yongzhan Nie, Kaichun Wu
Journal: Journal of Hepatology (2012)
Is There a Need to Further Subclassify pT2 Renal Cell Cancers as Implemented by the Revised 7th TNM Version?
Authors: Sandra Waalkes, Frank Becker, Andres J. Schrader, Martin Janssen, Gerd Wegener, Axel S. Merseburger, Mark Schrader, Rainer Hofmann, Michael Stöckle, Markus A. Kuczyk
Journal: European Urology (2010)
Disseminated Mycobacterium avium-intracellulare Infection in Homosexual Men Dying of Acquired Immunodeficiency
Authors: Phillip Zakowski
Journal: JAMA (1982)

Five homosexual men dying at UCLA Center for the Health Sciences, Los Angeles, with acquired immunodeficiency and<i>Pneumocystis</i>pneumonia, Kaposi's sarcoma, or cryptosporidiosis since May 1981 have all had mycobacteria of the Mycobacterium<i>avium-intracellulare</i>complex cultured from tissues taken just before death or at postmortem examination. Each man had histological evidence of disseminated mycobacterial infection. Acid-fast organisms were seen in macrophages in the lung, spleen, and lymph nodes in all cases and in a variety of additional organs in two cases. Other severe infections were always found at postmortem examination — cytomegalovirus, cryptosporidiosis, and<i>Pneumocystis</i>. Disseminated M<i>avium-intracellulare</i>infection has been so striking in homosexual males dying with acquired immunodeficiency at our institution that we believe a vigorous search for mycobacteria should be made in all such patients. Empiric therapy for mycobacterial infection may be justified in selected cases of immunodeficiency before a specific microbiological diagnosis. (<i>JAMA</i>1982;248:2980-2982)